Chronic increases in the availability of nutrients are likely to contribute to several key metabolic features of aging. The latter include (but are not limited to) increased deposition of fat within the abdominal cavity (visceral adiposity), increased tissue levels of triglycerides, insulin resistance, relative decrease in energy expenditure, and augmented risks for atherosclerotic disease (ASCVD) and for type 2 diabetes mellitus (DM2). Under normal circumstances, the deleterious effects of the excessive availability of nutrients are countered by the prompt activation of nutrient "counter regulatory" systems. The latter include (but are not limited to) hypothalamic neuro-circuitries partly under the control of leptin. The activation of these nutrient "counter regulatory" systems should prevent the excessive storage of energy and the onset of insulin resistance. Thus, there appears to be a functional feedback loop, which normally prevents visceral adiposity, insulin resistance, and other metabolic features of aging from developing. However, there is mounting evidence that aging is a state of leptin resistance. Consistent with these recent findings, the operation of this feedback loop is likely to be impaired and leptin may therefore fail to compensate for the deleterious effects of nutrient excess during the aging process. Our proposal will therefore focus on mechanisms responsible for hypothalamic responses to nutrient excess and how they are altered during aging. We also wish to discern impairments in hypothalamic neuro-circuitries, which are due to chronic increases in nutrient availability from those due to the aging process per se. Based on preliminary results and on this overall hypothesis we wish to pursue the following specific aims: Does aging modify the actions of leptin on energy, glucose and lipid metabolism and on insulin action? We will examine the dose-response relationship between central delivery of leptin and biological outcomes. We will particularly focus on the effect of low dose ICV leptin administration on metabolic rather than behavioral end points. Can stimulation of the melanocortin pathway overcome the leptin resistance of aging? We will test the hypothesis that activation of CNS melanocortin receptors bypasses the defect in leptin signaling in aging rats.